Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Dihydrofolate reductase

Gene

Dhfr

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway (PubMed:25980602). Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis (PubMed:25980602). Binds its own mRNA.By similarity1 Publication

Catalytic activityi

5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH.PROSITE-ProRule annotation2 Publications

Pathwayi: tetrahydrofolate biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate.
Proteins known to be involved in this subpathway in this organism are:
  1. Dihydrofolate reductase (Dhfr)
This subpathway is part of the pathway tetrahydrofolate biosynthesis, which is itself part of Cofactor biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate, the pathway tetrahydrofolate biosynthesis and in Cofactor biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei10NADP; via amide nitrogen and carbonyl oxygen2 Publications1
Binding sitei65Substrate1 Publication1
Binding sitei71Substrate1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi16 – 22NADP2 Publications7
Nucleotide bindingi55 – 57NADP2 Publications3
Nucleotide bindingi77 – 79NADP2 Publications3
Nucleotide bindingi117 – 124NADP2 Publications8

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase, RNA-binding
Biological processMethotrexate resistance, One-carbon metabolism
LigandNADP

Enzyme and pathway databases

BRENDAi1.5.1.3 3474
ReactomeiR-MMU-196757 Metabolism of folate and pterines
SABIO-RKiP00375
UniPathwayi
UPA00077;UER00158

Names & Taxonomyi

Protein namesi
Recommended name:
Dihydrofolate reductase (EC:1.5.1.32 Publications)
Gene namesi
Name:Dhfr
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:94890 Dhfr

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Mitochondrion

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL4564

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00001863642 – 187Dihydrofolate reductaseAdd BLAST186

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei33N6-acetyllysine; alternateCombined sources1
Modified residuei33N6-succinyllysine; alternateCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP00375
PaxDbiP00375
PeptideAtlasiP00375
PRIDEiP00375

PTM databases

iPTMnetiP00375
PhosphoSitePlusiP00375

Expressioni

Gene expression databases

BgeeiENSMUSG00000021707 Expressed in 283 organ(s), highest expression level in telencephalon
CleanExiMM_DHFR
ExpressionAtlasiP00375 baseline and differential
GenevisibleiP00375 MM

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

IntActiP00375, 2 interactors
MINTiP00375
STRINGi10090.ENSMUSP00000022218

Chemistry databases

BindingDBiP00375

Structurei

Secondary structure

1187
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP00375
SMRiP00375
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP00375

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 185DHFRPROSITE-ProRule annotationAdd BLAST182

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni31 – 36Substrate binding1 Publication6

Sequence similaritiesi

Belongs to the dihydrofolate reductase family.Curated

Phylogenomic databases

eggNOGiKOG1324 Eukaryota
COG0262 LUCA
GeneTreeiENSGT00390000010283
HOGENOMiHOG000040235
HOVERGENiHBG000773
InParanoidiP00375
KOiK00287
OMAiRDNQLPW
OrthoDBiEOG091G0PRK
PhylomeDBiP00375
TreeFamiTF317636

Family and domain databases

CDDicd00209 DHFR, 1 hit
Gene3Di3.40.430.10, 1 hit
InterProiView protein in InterPro
IPR024072 DHFR-like_dom_sf
IPR017925 DHFR_CS
IPR001796 DHFR_dom
PfamiView protein in Pfam
PF00186 DHFR_1, 1 hit
SUPFAMiSSF53597 SSF53597, 1 hit
PROSITEiView protein in PROSITE
PS00075 DHFR_1, 1 hit
PS51330 DHFR_2, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P00375-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MVRPLNCIVA VSQNMGIGKN GDLPWPPLRN EFKYFQRMTT TSSVEGKQNL
60 70 80 90 100
VIMGRKTWFS IPEKNRPLKD RINIVLSREL KEPPRGAHFL AKSLDDALRL
110 120 130 140 150
IEQPELASKV DMVWIVGGSS VYQEAMNQPG HLRLFVTRIM QEFESDTFFP
160 170 180
EIDLGKYKLL PEYPGVLSEV QEEKGIKYKF EVYEKKD
Length:187
Mass (Da):21,606
Last modified:January 23, 2007 - v3
Checksum:i47AEF15F879B119C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti4P → A in AAA37637 (PubMed:2982814).Curated1
Sequence conflicti14N → D in CAA39544 (PubMed:2263462).Curated1
Sequence conflicti123Q → E AA sequence (PubMed:762074).Curated1
Sequence conflicti123Q → E in AAA37525 (PubMed:360074).Curated1
Sequence conflicti124E → Q AA sequence (PubMed:762074).Curated1
Sequence conflicti128Q → E AA sequence (PubMed:762074).Curated1
Sequence conflicti174K → D AA sequence (PubMed:762074).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti23L → R in a form with an abnormally low affinity for methotrexate. 1 Publication1
Natural varianti32F → W in L-5178-Y cell line; methotrexate-resistant, requires 2 nucleotide substitutions. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
V00734 mRNA Translation: CAA24112.1
X56066 mRNA Translation: CAA39544.1
BC005796 mRNA Translation: AAH05796.1
M10071 Genomic DNA Translation: AAA37637.1
L26316 mRNA Translation: AAA37523.1
J00387
, J00382, J00383, J00384, J00385, J00386 Genomic DNA Translation: AAA37638.1
V00731 mRNA Translation: CAB43539.2
M10722 mRNA Translation: AAA37524.1
M10811 mRNA Translation: AAA37525.1
V00733 Genomic DNA Translation: CAA24111.1
CCDSiCCDS26680.1
PIRiS13096 RDMSD
RefSeqiNP_034179.1, NM_010049.3
UniGeneiMm.23695

Genome annotation databases

EnsembliENSMUST00000022218; ENSMUSP00000022218; ENSMUSG00000021707
GeneIDi13361
KEGGimmu:13361
UCSCiuc007rkl.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
V00734 mRNA Translation: CAA24112.1
X56066 mRNA Translation: CAA39544.1
BC005796 mRNA Translation: AAH05796.1
M10071 Genomic DNA Translation: AAA37637.1
L26316 mRNA Translation: AAA37523.1
J00387
, J00382, J00383, J00384, J00385, J00386 Genomic DNA Translation: AAA37638.1
V00731 mRNA Translation: CAB43539.2
M10722 mRNA Translation: AAA37524.1
M10811 mRNA Translation: AAA37525.1
V00733 Genomic DNA Translation: CAA24111.1
CCDSiCCDS26680.1
PIRiS13096 RDMSD
RefSeqiNP_034179.1, NM_010049.3
UniGeneiMm.23695

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1U70X-ray2.50A2-187[»]
2FZJX-ray2.00A2-187[»]
3D80X-ray1.40A2-187[»]
3D84X-ray1.90X2-187[»]
3K45X-ray1.60A2-187[»]
3K47X-ray2.05A2-187[»]
ProteinModelPortaliP00375
SMRiP00375
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP00375, 2 interactors
MINTiP00375
STRINGi10090.ENSMUSP00000022218

Chemistry databases

BindingDBiP00375
ChEMBLiCHEMBL4564

PTM databases

iPTMnetiP00375
PhosphoSitePlusiP00375

Proteomic databases

EPDiP00375
PaxDbiP00375
PeptideAtlasiP00375
PRIDEiP00375

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000022218; ENSMUSP00000022218; ENSMUSG00000021707
GeneIDi13361
KEGGimmu:13361
UCSCiuc007rkl.1 mouse

Organism-specific databases

CTDi1719
MGIiMGI:94890 Dhfr

Phylogenomic databases

eggNOGiKOG1324 Eukaryota
COG0262 LUCA
GeneTreeiENSGT00390000010283
HOGENOMiHOG000040235
HOVERGENiHBG000773
InParanoidiP00375
KOiK00287
OMAiRDNQLPW
OrthoDBiEOG091G0PRK
PhylomeDBiP00375
TreeFamiTF317636

Enzyme and pathway databases

UniPathwayi
UPA00077;UER00158

BRENDAi1.5.1.3 3474
ReactomeiR-MMU-196757 Metabolism of folate and pterines
SABIO-RKiP00375

Miscellaneous databases

ChiTaRSiDhfr mouse
EvolutionaryTraceiP00375
PROiPR:P00375
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000021707 Expressed in 283 organ(s), highest expression level in telencephalon
CleanExiMM_DHFR
ExpressionAtlasiP00375 baseline and differential
GenevisibleiP00375 MM

Family and domain databases

CDDicd00209 DHFR, 1 hit
Gene3Di3.40.430.10, 1 hit
InterProiView protein in InterPro
IPR024072 DHFR-like_dom_sf
IPR017925 DHFR_CS
IPR001796 DHFR_dom
PfamiView protein in Pfam
PF00186 DHFR_1, 1 hit
SUPFAMiSSF53597 SSF53597, 1 hit
PROSITEiView protein in PROSITE
PS00075 DHFR_1, 1 hit
PS51330 DHFR_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDYR_MOUSE
AccessioniPrimary (citable) accession number: P00375
Secondary accession number(s): P70693
, Q61485, Q61487, Q61579
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: January 23, 2007
Last modified: September 12, 2018
This is version 169 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again